Culture of brain tumor patient peripheral blood lymphocytes (PBL) with recombinant interleukin-2 (IL-2) results in the activation of lymphokine activated killer cells (LAK) with the capacity to lyse autologous and allogeneic glioblastoma. PBL obtained from brain tumor patients were cultured with or without IL-2 for three to seven days and then tested for their ability to lyse target cells in a 4-hour chromium release cytotoxicity assay. PBL were drawn one to two weeks following operative tumor debulking. Cells used as targets included fresh brain tumor cells obtained at the time of craniotomy, fresh brain tumor grown from one to three weeks in tissue culture, fresh autologous PBL and allogeneic glioblastoma grown in tissue culture. Brain tumor patient PBL cultured without IL-2 did not significantly lyse autologous or allogeneic glioblastoma. However, when these PBL were cultured with IL-2, LAK was generated which produced marked lysis of autologous as well as allogeneic tissue culture glioblastoma in all of eight cases. Significant lysis of autologous fresh tumor by patient LAK was observed in four of five experiments. By contrast, patient's LAK did not kill autologous normal PBL. The ability to generate LAK was not influenced by patient age, previous therapy or the administration of steroids. Eleven patients have received either IL-2 or LAK cells into their brain tissue at the time of surgical debulking of confirmed glioma. No toxicities have been observed.